The Importance of Clinical Examination under General Anesthesia: Improving Parametrial Assessment in Cervical Cancer Patients

Background: Parametrial tumor involvement is an important prognostic factor in cervical cancer and is used to guide management. Here, we investigate the diagnostic value of clinical examination under general anesthesia (EUA) and magnetic resonance imaging (MRI) in determining parametrial tumor spread. Methods: Post-operative pathological findings of 400 patients with primary cervical cancer were compared to the respective MRI data and the results from EUA. The gynecological oncologist had access to the MR images during clinical assessment (augmented EUA, aEUA). Results: Pathologically proven parametrial tumor invasion was present in 165 (41%) patients. aEUA exhibited a higher accuracy than MRI alone (83% vs. 76%; McNemar’s odds ratio [OR] = 2.0, 95%CI 1.25–3.27, p = 0.003). Although accuracy was not affected by tumor size in aEUA, MRI was associated with a lower accuracy in tumors ≥2.5 cm (OR for a correct diagnosis compared to smaller tumors 0.22, p < 0.001). There was also a decrease in specificity when evaluating parametrial invasion by MRI in tumors ≥2.5 cm in diameter (p < 0.0001) compared to smaller tumors (< 2.5 cm). Body mass index had no influence on performance of either method. Conclusions: aEUA has the potential to increase the diagnostic accuracy of MRI in determining parametrial tumor involvement in cervical cancer patients.

Utilization and outcomes of adjuvant systemic chemotherapy alone in high risk, early stage cervical cancer in the United States

ObjectiveTo examine trends and outcomes related to adjuvant systemic chemotherapy alone for high risk, early stage cervical cancer.MethodsThis retrospective observational study queried the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program from 2000 to 2016. Surgically treated women with American Joint Commission on Cancer stages T1–2 cervical cancer who had high risk factors (nodal metastasis and/or parametrial invasion) and received additional therapy were examined. Propensity score inverse probability of treatment weighting was used to assess the survival estimates for systemic chemotherapy versus external beam radiotherapy with chemotherapy.ResultsAmong 2462 patients with high risk factors, 185 (7.5%) received systemic chemotherapy without external beam radiotherapy, of which the utilization significantly increased over time in multivariable analysis (adjusted odds ratio per 1 year increment 1.06, 95% confidence interval (CI) 1.02 to 1.09). In weighted models, adjuvant chemotherapy and combination therapy (external beam radiotherapy and chemotherapy) had comparable overall survival among patients aged <40 years (hazard ratio (HR) 0.73, 95% CI 0.41 to 1.33), in adenocarcinoma or adenosquamous histologies (HR 0.90, 95% CI 0.62 to 1.32), and in those with nodal metastasis alone without parametrial tumor invasion (HR 1.17, 95% CI 0.84 to 1.62). In contrast, systemic chemotherapy alone was associated with increased all cause mortality compared with combination therapy in patients aged ≥40 years (HR 1.57, 95% CI 1.19 to 2.06), with squamous histology (HR 1.63, 95% CI 1.19 to 2.22), and with parametrial invasion alone (HR 1.87, 95% CI 1.09 to 3.20) or parametrial invasion with nodal metastasis (HR 1.64, 95% CI 1.06 to 2.52).ConclusionUtilization of adjuvant systemic chemotherapy alone for high risk, early stage cervical cancer is increasing in the United States in the recent years. Our study suggests that survival effects of adjuvant systemic chemotherapy may vary based on patient and tumor factors. External beam radiotherapy with chemotherapy remains the standard for high risk, early stage cervical cancer, and use of adjuvant systemic chemotherapy without external beam radiotherapy should be considered with caution.

Utilization and outcome of systemic chemotherapy for high-risk early-stage cervical cancer.

e17521 Background: To examine trends and outcomes of systemic chemotherapy for high-risk early-stage cervical cancer. Methods: This retrospective observational study queried the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program from 2000-2016. Surgically-treated women with stage T1-2 cervical cancer who had high-risk factors (lymph node metastasis and/or parametrial invasion) and received adjuvant therapy were examined. Propensity score inverse probability of treatment weighting was used to assess the survival estimates for chemotherapy use versus external beam with chemotherapy (CCRT). Results: Among 2, 462 women with high-risk factor, 185 (7.5%) received systemic chemotherapy. Utilization of chemotherapy has significantly increased over time in multivariable analysis (adjusted-odds ratio per 1-year increment, 1.06, 95% confidence interval [CI] 1.02-1.09). In weighted models, adjuvant chemotherapy and CCRT had comparable survival among women aged < 40 (hazard ratio [HR] for all-cause mortality 0.73, 95%CI 0.41-1.33), adenocarcinoma or adenosquamous histologies (HR 0.90, 95%CI 0.62-1.32), and high-risk group based on nodal metastasis alone (HR 1.17, 95%CI 0.84-1.62). In contrast, chemotherapy was associated with increased all-cause mortality compared to CCRT among women aged ≥40 (HR 1.57, 95%CI 1.19-2.06), squamous histology (HR 1.63, 95%CI 1.19-2.22), and high-risk group per parametrial invasion alone (HR 1.87, 95%CI 1.09-3.20) or parametrial invasion with nodal metastasis (HR 1.64, 95%CI 1.06-2.52). Conclusions: Utilization of systemic chemotherapy for high-risk early-stage cervical cancer is increasing in the United States. Survival effects of adjuvant chemotherapy varied per patient and tumor factors, and this indication may be limited to those who are < 40 years with non-squamous histology and absence of parametrial invasion.

Uterus Preservation Versus Caesarean Hysterectomy in Management of Placenta Accreta Spectrum: A Multicentre International Study

Objective: To compare peripartum outcomes of uterus preserving procedures to caesarean hysterectomy in women with placenta accreta spectrum (PAS), and to identify risk factors associated with adverse maternal outcomes. Design: Retrospective study (ClinicalTrials.gov identifier: NCT04384510) Setting:11 tertiary centres from 9 countries Population or Sample: women with of PAS who were managed in participating centres between January 1st, 2010 and December 31st, 2019. Women who had confirmed diagnosis with PAS with adequate documentation and follow-up, were considered eligible. Main Outcome Measures: Primary outcome was massive PAS-associated perioperative blood loss (intraoperative blood loss ≥ 2500 ml, bleeding associated massive transfusion protocol, or complicated by disseminated intravascular coagulopathy). Results: Out of 797 women, 727 were eligible for the study. Five hundred ninety-two (81.43%) women were managed by uterus preserving procedures versus 135 (18.56%) who underwent caesarean hysterectomy. After adjustment for significant or close-to-significance variables, type of management was not associated with higher risk of massive blood loss (aOR 1.71, 95% CI 0.78 - 3.81). Other factors that were significantly associated with higher risk of massive PAS-associated blood loss included body mass index, preoperative haemoglobin, centrally located placenta, diffuse placental invasion, parametrial invasion, and intrauterine foetal death. Conclusions: In the presence of sufficient experience, uterus preserving procedures may not be associated with higher risk of massive blood loss compared to caesarean hysterectomy. Funding: none

Topographic distribution of lymph node metastasis in patients with stage IB1 cervical cancer: an analysis of 8314 lymph nodes

Background Systematic pelvic lymphadenectomy or whole pelvic irradiation is recommended for the patients with stage IB1 cervical cancer. However, the precise pattern of lymphatic tumor spread in cervical cancer is unknown. In the present study we evaluated the distribution of nodal metastases in stage IB1 cervical cancer to explore the possibilities for tailoring cancer treatment. Methods A total of 289 patients with cervical cancer of stage IB1, according to FIGO 2009, were retrospectively analyzed. All patients underwent laparoscopic radical hysterectomy (Querleu and Morrow type C2) and systematic pelvic lymphadenectomy with or without para-aortic lymphadenectomy (level 2 or level 3 according to Querleu and Morrow) from October 2014 to December 2017. Lymph nodes removed from 7 well-defined anatomical locations as well as other tissues were examined histopathologically, and typed, graded, and staged according to the WHO/IARC classification. Results Totally 8314 lymph nodes were analyzed with the average number of 31.88 ± 10.34 (Mean ± SD) lymph nodes per patient. Nodal metastases were present in 44 patients (15.22%). The incidence of lymphatic spread to different anatomic sites ranged from 0% (presacral) to 30.92% (obturator nodes). Tumor size above 2 cm, histologically proven lymphovascular space involvement (LVSI) and parametrial invasion were shown to be significantly correlated with the higher risk of lymphatic metastasis, while obesity (BMI ≥ 25) was independently negatively associated with lymphatic metastases. Conclusions The incidence of lymph node metastasis in patients with stage IB1 cervical cancer is low but prognostically relevant. Individual treatment could be considered for the selected low-risk patients who have smaller tumors and obesity and lack of the parametrial invasion or LVSI.

Identification of risk factors associated with pelvic lymph node metastasis in patients with stage IB1 cervical cancer.

e18005 Background: Evaluation the distribution of nodal metastases in the stage IB1 cervical cancer and the risk factors associated with pelvic lymph node metastasis (LNM) at each anatomic location. Methods: 728 patients with stage IB1 cervical cancer who underwent radical hysterectomies and systemic pelvic lymphadenectomies from January 2008 to December 2017 were retrospectively studied. All removed pelvic lymph nodes were pathologically examined, and the risk factors for LNM at the obturator, internal iliac, external iliac, and common iliac regions were evaluated by univariate and multivariate logistic regression analyses. Results: 20,134 lymph nodes were analysed with the average number of 27.80 (± SD 9.43) lymph nodes per patient. Nodal metastases were present in 266 (14.6%) patients. The obturator was the most common site for nodal metastasis (42.5%) followed by the internal iliac nodes (20.3%) and the external iliac nodes (19.9%), while the common iliac (9.8%) and parametrial (7.5%) nodes were the least likely to be involved. Tumor size more than 2 cm, histologically proven lymphovascular space involvement (LVSI) and parametrial invasion correlated independently significantly with the higher risk of the lymphatic metastasis. Obesity (BMI≥25) was independently significantly negatively correlated with the risk of lymphatic metastases. All the positive common iliac nodes were found in patients with tumors greater than 2 cm. The multivariate analysis showed that tumor size greater than 3 cm was associated with a 16.6-fold increase in the risk for common iliac LNM. Interestingly, tumor size was not an independent risk factor for pelvic LNM in the lower regions, i.e., the obturator, internal iliac and external iliac areas, where LVSI was the most significant predictor for LNM. In addition, parametrial invasion was related to external and internal iliac LNM; deep stromal invasion and age less than 50 years were associated with obturator LNM. Conclusions: The incidence of lymph node metastasis in patients with stage IB1 cervical cancer is low but prognostically relevant. The data offer the opportunity for tailored individual treatment in selected patients with small tumors and obesity.

Clinically Significant Discrepancy between Clinical and Pathologic Stage of Early Operable Cervical Cancer

Objectives: The cornerstone of the management of cervical cancer (CC) traditionally relies on clinical examination (CE) of tumor size (TS) and local extension of disease. The goal of this study is to determine the accuracy of CE in comparison to final pathology (FP) in early operable CC. Methods: This is a multi-center retrospective review of patients with early CC (FIGO 2009 Stage IB1, IIA1). CE of TS, parametrial invasion (PI), and vaginal involvement (VI) were compared to FP. Results: The final analysis included 135 patients. Overall, there was a significant difference between CE of TS compared to FP; mean error of 1.22 cm (p<0.0001). In tumors  2cm the mean error was 1.28 cm (p<0.0001). No significant discrepancy was observed in tumors <2 cm (mean error: 1.10cm; p=0.5). CE of TS of endophytic tumors was poor (mean error 1.68cm; p=0.004) compared to exophytic tumors (mean error: 1.12 cm; p=0.693). There was no significant difference in the identification of VI between CE and FP (3.7% vs. 8.89%; p=0.067). 14.07% of patients were found to have PI on FP (p<0.0001). There was no difference in the accuracy CE of TS between non-obese (<30 kg/m2 ) and obese patients (30 kg/m2 ) (p=0.061). As a result of FP, 55 patients (40.7%) received adjuvant RT and 38 patients (28.14%) were upstaged from IB1 to IB2. Conclusion: CE of TS and PI is inaccurate, especially in tumors  2cm and